Grazia Cifone | Università Degli Studi Dell'Aquila (original) (raw)
Papers by Grazia Cifone
International journal of immunopathology and pharmacology
Current management of atopic dermatitis is mainly directed to the reduction of cutaneous inflamma... more Current management of atopic dermatitis is mainly directed to the reduction of cutaneous inflammation. Since patients with atopic dermatitis show abnormalities in immunoregulation, a therapy aimed to adjust their immune function could represent an alternative approach, particularly in the severe form of the disease. Indeed, T-lymphocytes constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated T-cell induced keratinocyte apoptosis appears to be an important pathogenetic factor of the eczematous disease. In recent years, attention has been focused on the interaction between host and probiotics which may have anti-inflammatory properties and immunomodulatory activities. The aim of the present work is to investigate the effect of a selected probiotic extract, the Bifidobacterium infantis extract, on a human keratinocyte cell line (HaCaT) abnormal apoptosis induced by activated-T-lymphocyte. An in vitro model of atopic dermatitis was used t...
Biomolecules, 2019
A growing body of evidence supports the use of probiotics in the treatment of several skin condit... more A growing body of evidence supports the use of probiotics in the treatment of several skin conditions, including wounds. Even if in vitro and in vivo studies have highlighted the pro-healing effects of some probiotic bacteria, the underlying mechanisms are still not fully defined. The current investigation aimed to determine the re-epithelialization potential of the soluble fraction from lysate of seven different probiotic strains belonging to different genera (i.e., Streptococcus, Lactobacillus, and Bifidobacterium) on in vitro physically wounded HaCaT monolayer model. The results suggested that the soluble fraction of S. thermophilus, L. plantarum, and L. acidophilus promoted the re-epithelialization of scratched HaCaT monolayers, whereas those from B. longum, B. infantis, and B. breve significantly inhibited the process. On the other hand, L. bulgaricus showed no significant effect on in vitro wound repair. The mechanisms underlying the pro- or anti-healing properties of selected...
The Neuroradiology Journal, 1999
Clinical and Experimental Immunology, 2001
SummarySystemic sclerosis (SSc) is a connective tissue disease in which immune system activation ... more SummarySystemic sclerosis (SSc) is a connective tissue disease in which immune system activation is evidenced by high levels of different cytokines in the sera and/or in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by the presence of specific autoantibodies. γ/δ T cells accumulate in the lung and the skin of SSc patients suggesting their potential role in the development and maintenance of the disease. The aim of this study was to assess cytokine production and cytotoxic activity of circulating γ/δ T lymphocytes obtained from SSc patients and to evaluate their potential role during this disorder. Our results showed that both the proportion and the absolute number of IFN-γγ/δ-producing cells (i.e. displaying a Th1 polarization) in SSc was significantly higher than either the proportion and the absolute number of IL-4 γ/δ-producing cells in SSc or the proportion and the absolute number of IFN-γγ/δ-producing cells in healthy controls (P < 0·05 for both ...
International Journal of Molecular Sciences, 2021
Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represen... more Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in ne...
Glutamate is the primary excitatory neurotransmitter in the brain. At the neuronal synapse, it in... more Glutamate is the primary excitatory neurotransmitter in the brain. At the neuronal synapse, it interacts with a variety of receptors that specify neurotransmitter interactions and transmit information into target cells. The vast majority of synapses in the central nervous system use glutamate as a neurotransmitter to produce rapid neuronal excitation. I,2 Glutamate neurotransmission also participates in neuronal plasticity and neurotoxicity. Neuronal plasticity elicited by glutamate is exemplified by long-term potentiation (LTP) in the hippocampus3 and long term depression in the cerebellum.4 However, at supraphysiological concentrations, it is a potent excitotoxin that causes neuronal death through a cascade of cationic and second messenger events.5,6 In fact, in many neurologic disorders, injury to neurons may be partly caused by overstimulation of receptors for excitatory amino acids, including glutamate and aspartate. These neurologic conditions range from acute insults such as ...
Cell Death & Differentiation, 1999
Regulation of T-cell survival is a physiological process involved in determining the immune respo... more Regulation of T-cell survival is a physiological process involved in determining the immune response development, and also the expansion of T-cell tumours. Glucocorticoid hormones (GCH) have been implicated as regulators of Tlymphocyte growth and differentiation. In particular, GCH which by themselves are apoptosis activators and induce Tcell death, can also counteract apoptosis activated by other stimuli, for example antigen-TCR interaction. A number of biochemical events constitute different GCH-activated deathtriggering pathways and transcription activity regulation, either upstream and/or downstream in the pathways, is essential to apoptosis. Similarly, GCH-mediated inhibition of apoptosis also requires gene transcription regulation. In particular, between a number of GCH-induced genes, GITR and GILZ can inhibit apoptosis through interaction with mechanisms involved in T-cell survival regulation including the NF-kB transcription activity and the expression of the Fas/ FasL system. These observations indicate that this GCHactivated dual effect, induction and/or inhibition of T-cell death, requires transcription regulation.
Archives of Internal Medicine, 1999
We read with great interest the recent article by Fairfield and colleagues. 1 We agree with their... more We read with great interest the recent article by Fairfield and colleagues. 1 We agree with their conclusions that appropriate investigations are necessary to establish with confidence the benefit or risk associated with the use of complementary and alternative medicine by persons ...
Journal of Cellular Physiology, 2015
† This article has been accepted for publication and undergone full peer review but has not been ... more † This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Biomedicine & Pharmacotherapy
BioMed Research International
The ability of a collagen-based matrix to support cell proliferation, migration, and infiltration... more The ability of a collagen-based matrix to support cell proliferation, migration, and infiltration has been reported; however, the direct effect of an aqueous collagen suspension on cell cultures has not been studied yet. In this work, the effects of a high-concentration aqueous suspension of a micronized type I equine collagen (EC-I) have been evaluated on a normal mouse fibroblast cell line. Immunofluorescence analysis showed the ability of EC-I to induce a significant increase of type I and III collagen levels, parallel with overexpression of crucial proteins in collagen biosynthesis, maturation, and secretion, prolyl 4-hydroxylase (P4H) and heat shock protein 47 (HSP47), as demonstrated by western blot experiments. The treatment led, also, to an increase of α-smooth muscle actin (α-SMA) expression, evaluated through western blot analysis, and cytoskeletal reorganization, as assessed by phalloidin staining. Moreover, scanning electron microscopy analysis highlighted the appearance...
Nutrients
Background: Nickel (Ni) oral consumption may elicit systemic reactions in patients affected by sy... more Background: Nickel (Ni) oral consumption may elicit systemic reactions in patients affected by systemic nickel allergy syndrome (SNAS), including gastrointestinal symptoms, which in turn are associated with gut dysbiosis. We evaluated the effects of a low-Ni diet alone or in combination with the oral consumption of appropriate probiotics on Ni-sensitivity and urinary dysbiosis markers in SNAS patients. Methods: n = 51 patients with SNAS and concomitant intestinal dysbiosis were enrolled in the study. According to the urinary indican/skatole levels, quantified through a colorimetric and a high-performance liquid chromatographic method, respectively, patients were assigned to a dysbiosis type/grade and followed a low-Ni diet for three months. Along with the diet, 22 patients also consumed probiotics based on the dysbiosis type. In particular, a Lactobacilli- or Bifidobacteria-containing formulation was administered to patients with fermentative or putrefactive dysbiosis, respectively,...
American Journal of Gastroenterology
Oncotarget, Jan 15, 2018
Chemotherapy-induced peripheral neuropathy (CIPN) is a widespread and potentially disabling side ... more Chemotherapy-induced peripheral neuropathy (CIPN) is a widespread and potentially disabling side effect of various anticancer drugs. In spite of the intensive research focused on obtaining therapies capable to treat or prevent CIPN, the medical demand remains very high. Microtubule-stabilizing agents, among which taxanes, are effective chemotherapeutic agents for the therapy of several oncologic diseases. The inflammatory process activated by chemotherapeutic agents has been interpreted as a potential trigger of the nociceptive process in CIPN. The chemotherapy-driven release of proinflammatory and chemokines has been recognized as one of the principal mechanisms controlling the establishment of CIPN. Several reports have indicated that probiotics are capable to regulate the balance of anti-inflammatory and pro-inflammatory cytokines. Accordingly, it has been suggested that some probiotic formulations, may have an effective role in the management of inflammatory pain symptoms. Exper...
Journal of cellular physiology, 2017
Glioblastoma (GB) is the most common cancer in the brain and with an increasing incidence. Despit... more Glioblastoma (GB) is the most common cancer in the brain and with an increasing incidence. Despite major advances in the field, there is no curative therapy for GB to date. Many solid tumors, including GB, experienced metabolic reprogramming in order to sustain uncontrolled proliferation, hypoxic conditions, and angiogenesis. PPARs, member of the steroid hormone receptor superfamily, are particularly involved in the control of energetic metabolism, particularly lipid metabolism, which has been reported deregulated in gliomas. PPARα was previously indicated by us as a potential therapeutic target for this neoplasm, due to the malignancy grade dependency of its expression, being particularly abundant in GB. In this work, we used a new PPARα antagonist on patient-derived GB primary cells, with particular focus on the effects on lipid metabolism and response to radiotherapy. The results obtained demonstrated that blocking PPARα results in cell death induction, increase of radiosensitivi...
Journal of Cellular Physiology, 2017
The data here reported introduce the wound-healing assay as a tool for testing probiotics aimed a... more The data here reported introduce the wound-healing assay as a tool for testing probiotics aimed at protecting gastrointestinal mucosal surfaces and to verify the consistency of their manufacturing. At the scope, we compared the in vitro effects of two multi-strain high concentration formulations both commercialized under the same brand VSL#3 but sourced from different production sites (USA and Italy) on a non-transformed small-intestinal epithelial cell line, IEC-6. The effects on cellular morphology, viability, migration, and H2 O2 -induced damage, were assessed before and after the treatment with both VSL#3 formulations. While the USA-sourced product (&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) VSL#3 did not affect monolayer morphology and cellular density, the addition of bacteria from the Italy-derived product (&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) VSL#3 caused clear morphological cell damage and strongly reduced cellularity. The treatment with &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; lysate led to a higher rate of wounded monolayer healing, while the addition of &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; bacterial lysate did not influence the closure rate as compared to untreated cells. While lysates from &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; VSL#3 clearly enhanced the formation of elongated and aligned stress fibers, &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; lysates had not similar effect. &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; lysate was able to cause a total inhibition of H2 O2 -induced cytotoxic effect whereas &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; VSL#3 lysate was unable to protect IEC-6 cells from H2 O2 -induced damage. ROS generation was also differently influenced, thus supporting the hypotesis of a protective action of &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; VSL#3 lysates, as well as the idea that &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; formulation was unable to prevent significantly the H2 O2 -induced oxidative stress.
PLOS ONE, 2016
A careful selection of the probiotic agent, standardization of the dose and detailed characteriza... more A careful selection of the probiotic agent, standardization of the dose and detailed characterization of the beneficial effects are essential when considering use of a probiotic for the dietary management of serious diseases. However, changes in the manufacturing processes, equipment or facilities can result in differences in the product itself due to the live nature of probiotics. The need to reconfirm safety and/or efficacy for any probiotic product made at a different factory is therefore mandatory. Recently, under the brand VSL#31, a formulation produced by a manufacturer different from the previous one, has been commercialized in some European countries (the UK and Holland). VSL#3 is a high concentration multi-strain preparation which has been recognized by the main Gastroenterology Associations for the dietary management of pouchitis as well as ulcerative colitis. We have compared the "original" VSL#3 produced in USA with the "newfound" VSL#3 produced in Italy. According to our results, the "newfound" VSL#3 has 130-150% more "dead bacteria" compared to the "original" product, raising concerns for the well-known association between dead microbes with adverse effects. The abilities of bacterial lysates from the two formulations to influence in vitro viability and proliferation of different tumor cell lines also resulted different. The repair of previously scratched monolayers of various adherent tumor cell lines (i.e. HT1080, and Caco-2 cells) was inhibited more significantly by the "original" VSL#3 when compared to the "newfound" VSL#3. Tumor cell cycle profile, in particular cell cycle arrest and apoptotic death of the cancer cells, further confirms that the "original" VSL#3 has a better functional profile than the "newfound" VSL#3, at least in in vitro. Our data stress the importance of the production conditions for the "newfound" VSL#3 considering that this product is intended to be used for the dietary management of patients with very serious diseases, such as chronic inflammatory bowel diseases.
International journal of immunopathology and pharmacology
Current management of atopic dermatitis is mainly directed to the reduction of cutaneous inflamma... more Current management of atopic dermatitis is mainly directed to the reduction of cutaneous inflammation. Since patients with atopic dermatitis show abnormalities in immunoregulation, a therapy aimed to adjust their immune function could represent an alternative approach, particularly in the severe form of the disease. Indeed, T-lymphocytes constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated T-cell induced keratinocyte apoptosis appears to be an important pathogenetic factor of the eczematous disease. In recent years, attention has been focused on the interaction between host and probiotics which may have anti-inflammatory properties and immunomodulatory activities. The aim of the present work is to investigate the effect of a selected probiotic extract, the Bifidobacterium infantis extract, on a human keratinocyte cell line (HaCaT) abnormal apoptosis induced by activated-T-lymphocyte. An in vitro model of atopic dermatitis was used t...
Biomolecules, 2019
A growing body of evidence supports the use of probiotics in the treatment of several skin condit... more A growing body of evidence supports the use of probiotics in the treatment of several skin conditions, including wounds. Even if in vitro and in vivo studies have highlighted the pro-healing effects of some probiotic bacteria, the underlying mechanisms are still not fully defined. The current investigation aimed to determine the re-epithelialization potential of the soluble fraction from lysate of seven different probiotic strains belonging to different genera (i.e., Streptococcus, Lactobacillus, and Bifidobacterium) on in vitro physically wounded HaCaT monolayer model. The results suggested that the soluble fraction of S. thermophilus, L. plantarum, and L. acidophilus promoted the re-epithelialization of scratched HaCaT monolayers, whereas those from B. longum, B. infantis, and B. breve significantly inhibited the process. On the other hand, L. bulgaricus showed no significant effect on in vitro wound repair. The mechanisms underlying the pro- or anti-healing properties of selected...
The Neuroradiology Journal, 1999
Clinical and Experimental Immunology, 2001
SummarySystemic sclerosis (SSc) is a connective tissue disease in which immune system activation ... more SummarySystemic sclerosis (SSc) is a connective tissue disease in which immune system activation is evidenced by high levels of different cytokines in the sera and/or in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by the presence of specific autoantibodies. γ/δ T cells accumulate in the lung and the skin of SSc patients suggesting their potential role in the development and maintenance of the disease. The aim of this study was to assess cytokine production and cytotoxic activity of circulating γ/δ T lymphocytes obtained from SSc patients and to evaluate their potential role during this disorder. Our results showed that both the proportion and the absolute number of IFN-γγ/δ-producing cells (i.e. displaying a Th1 polarization) in SSc was significantly higher than either the proportion and the absolute number of IL-4 γ/δ-producing cells in SSc or the proportion and the absolute number of IFN-γγ/δ-producing cells in healthy controls (P < 0·05 for both ...
International Journal of Molecular Sciences, 2021
Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represen... more Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in ne...
Glutamate is the primary excitatory neurotransmitter in the brain. At the neuronal synapse, it in... more Glutamate is the primary excitatory neurotransmitter in the brain. At the neuronal synapse, it interacts with a variety of receptors that specify neurotransmitter interactions and transmit information into target cells. The vast majority of synapses in the central nervous system use glutamate as a neurotransmitter to produce rapid neuronal excitation. I,2 Glutamate neurotransmission also participates in neuronal plasticity and neurotoxicity. Neuronal plasticity elicited by glutamate is exemplified by long-term potentiation (LTP) in the hippocampus3 and long term depression in the cerebellum.4 However, at supraphysiological concentrations, it is a potent excitotoxin that causes neuronal death through a cascade of cationic and second messenger events.5,6 In fact, in many neurologic disorders, injury to neurons may be partly caused by overstimulation of receptors for excitatory amino acids, including glutamate and aspartate. These neurologic conditions range from acute insults such as ...
Cell Death & Differentiation, 1999
Regulation of T-cell survival is a physiological process involved in determining the immune respo... more Regulation of T-cell survival is a physiological process involved in determining the immune response development, and also the expansion of T-cell tumours. Glucocorticoid hormones (GCH) have been implicated as regulators of Tlymphocyte growth and differentiation. In particular, GCH which by themselves are apoptosis activators and induce Tcell death, can also counteract apoptosis activated by other stimuli, for example antigen-TCR interaction. A number of biochemical events constitute different GCH-activated deathtriggering pathways and transcription activity regulation, either upstream and/or downstream in the pathways, is essential to apoptosis. Similarly, GCH-mediated inhibition of apoptosis also requires gene transcription regulation. In particular, between a number of GCH-induced genes, GITR and GILZ can inhibit apoptosis through interaction with mechanisms involved in T-cell survival regulation including the NF-kB transcription activity and the expression of the Fas/ FasL system. These observations indicate that this GCHactivated dual effect, induction and/or inhibition of T-cell death, requires transcription regulation.
Archives of Internal Medicine, 1999
We read with great interest the recent article by Fairfield and colleagues. 1 We agree with their... more We read with great interest the recent article by Fairfield and colleagues. 1 We agree with their conclusions that appropriate investigations are necessary to establish with confidence the benefit or risk associated with the use of complementary and alternative medicine by persons ...
Journal of Cellular Physiology, 2015
† This article has been accepted for publication and undergone full peer review but has not been ... more † This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Biomedicine & Pharmacotherapy
BioMed Research International
The ability of a collagen-based matrix to support cell proliferation, migration, and infiltration... more The ability of a collagen-based matrix to support cell proliferation, migration, and infiltration has been reported; however, the direct effect of an aqueous collagen suspension on cell cultures has not been studied yet. In this work, the effects of a high-concentration aqueous suspension of a micronized type I equine collagen (EC-I) have been evaluated on a normal mouse fibroblast cell line. Immunofluorescence analysis showed the ability of EC-I to induce a significant increase of type I and III collagen levels, parallel with overexpression of crucial proteins in collagen biosynthesis, maturation, and secretion, prolyl 4-hydroxylase (P4H) and heat shock protein 47 (HSP47), as demonstrated by western blot experiments. The treatment led, also, to an increase of α-smooth muscle actin (α-SMA) expression, evaluated through western blot analysis, and cytoskeletal reorganization, as assessed by phalloidin staining. Moreover, scanning electron microscopy analysis highlighted the appearance...
Nutrients
Background: Nickel (Ni) oral consumption may elicit systemic reactions in patients affected by sy... more Background: Nickel (Ni) oral consumption may elicit systemic reactions in patients affected by systemic nickel allergy syndrome (SNAS), including gastrointestinal symptoms, which in turn are associated with gut dysbiosis. We evaluated the effects of a low-Ni diet alone or in combination with the oral consumption of appropriate probiotics on Ni-sensitivity and urinary dysbiosis markers in SNAS patients. Methods: n = 51 patients with SNAS and concomitant intestinal dysbiosis were enrolled in the study. According to the urinary indican/skatole levels, quantified through a colorimetric and a high-performance liquid chromatographic method, respectively, patients were assigned to a dysbiosis type/grade and followed a low-Ni diet for three months. Along with the diet, 22 patients also consumed probiotics based on the dysbiosis type. In particular, a Lactobacilli- or Bifidobacteria-containing formulation was administered to patients with fermentative or putrefactive dysbiosis, respectively,...
American Journal of Gastroenterology
Oncotarget, Jan 15, 2018
Chemotherapy-induced peripheral neuropathy (CIPN) is a widespread and potentially disabling side ... more Chemotherapy-induced peripheral neuropathy (CIPN) is a widespread and potentially disabling side effect of various anticancer drugs. In spite of the intensive research focused on obtaining therapies capable to treat or prevent CIPN, the medical demand remains very high. Microtubule-stabilizing agents, among which taxanes, are effective chemotherapeutic agents for the therapy of several oncologic diseases. The inflammatory process activated by chemotherapeutic agents has been interpreted as a potential trigger of the nociceptive process in CIPN. The chemotherapy-driven release of proinflammatory and chemokines has been recognized as one of the principal mechanisms controlling the establishment of CIPN. Several reports have indicated that probiotics are capable to regulate the balance of anti-inflammatory and pro-inflammatory cytokines. Accordingly, it has been suggested that some probiotic formulations, may have an effective role in the management of inflammatory pain symptoms. Exper...
Journal of cellular physiology, 2017
Glioblastoma (GB) is the most common cancer in the brain and with an increasing incidence. Despit... more Glioblastoma (GB) is the most common cancer in the brain and with an increasing incidence. Despite major advances in the field, there is no curative therapy for GB to date. Many solid tumors, including GB, experienced metabolic reprogramming in order to sustain uncontrolled proliferation, hypoxic conditions, and angiogenesis. PPARs, member of the steroid hormone receptor superfamily, are particularly involved in the control of energetic metabolism, particularly lipid metabolism, which has been reported deregulated in gliomas. PPARα was previously indicated by us as a potential therapeutic target for this neoplasm, due to the malignancy grade dependency of its expression, being particularly abundant in GB. In this work, we used a new PPARα antagonist on patient-derived GB primary cells, with particular focus on the effects on lipid metabolism and response to radiotherapy. The results obtained demonstrated that blocking PPARα results in cell death induction, increase of radiosensitivi...
Journal of Cellular Physiology, 2017
The data here reported introduce the wound-healing assay as a tool for testing probiotics aimed a... more The data here reported introduce the wound-healing assay as a tool for testing probiotics aimed at protecting gastrointestinal mucosal surfaces and to verify the consistency of their manufacturing. At the scope, we compared the in vitro effects of two multi-strain high concentration formulations both commercialized under the same brand VSL#3 but sourced from different production sites (USA and Italy) on a non-transformed small-intestinal epithelial cell line, IEC-6. The effects on cellular morphology, viability, migration, and H2 O2 -induced damage, were assessed before and after the treatment with both VSL#3 formulations. While the USA-sourced product (&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) VSL#3 did not affect monolayer morphology and cellular density, the addition of bacteria from the Italy-derived product (&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) VSL#3 caused clear morphological cell damage and strongly reduced cellularity. The treatment with &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; lysate led to a higher rate of wounded monolayer healing, while the addition of &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; bacterial lysate did not influence the closure rate as compared to untreated cells. While lysates from &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; VSL#3 clearly enhanced the formation of elongated and aligned stress fibers, &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; lysates had not similar effect. &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; lysate was able to cause a total inhibition of H2 O2 -induced cytotoxic effect whereas &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; VSL#3 lysate was unable to protect IEC-6 cells from H2 O2 -induced damage. ROS generation was also differently influenced, thus supporting the hypotesis of a protective action of &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;USA-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; VSL#3 lysates, as well as the idea that &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Italy-made&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; formulation was unable to prevent significantly the H2 O2 -induced oxidative stress.
PLOS ONE, 2016
A careful selection of the probiotic agent, standardization of the dose and detailed characteriza... more A careful selection of the probiotic agent, standardization of the dose and detailed characterization of the beneficial effects are essential when considering use of a probiotic for the dietary management of serious diseases. However, changes in the manufacturing processes, equipment or facilities can result in differences in the product itself due to the live nature of probiotics. The need to reconfirm safety and/or efficacy for any probiotic product made at a different factory is therefore mandatory. Recently, under the brand VSL#31, a formulation produced by a manufacturer different from the previous one, has been commercialized in some European countries (the UK and Holland). VSL#3 is a high concentration multi-strain preparation which has been recognized by the main Gastroenterology Associations for the dietary management of pouchitis as well as ulcerative colitis. We have compared the "original" VSL#3 produced in USA with the "newfound" VSL#3 produced in Italy. According to our results, the "newfound" VSL#3 has 130-150% more "dead bacteria" compared to the "original" product, raising concerns for the well-known association between dead microbes with adverse effects. The abilities of bacterial lysates from the two formulations to influence in vitro viability and proliferation of different tumor cell lines also resulted different. The repair of previously scratched monolayers of various adherent tumor cell lines (i.e. HT1080, and Caco-2 cells) was inhibited more significantly by the "original" VSL#3 when compared to the "newfound" VSL#3. Tumor cell cycle profile, in particular cell cycle arrest and apoptotic death of the cancer cells, further confirms that the "original" VSL#3 has a better functional profile than the "newfound" VSL#3, at least in in vitro. Our data stress the importance of the production conditions for the "newfound" VSL#3 considering that this product is intended to be used for the dietary management of patients with very serious diseases, such as chronic inflammatory bowel diseases.